Iron is an essential nutrient for all microorganisms. In most circumstances free iron is unavailable for microbial growth, and this is especially true in body fluids and tissues. Many microorganisms have evolved the production of s small molecular weight compounds called siderophores, that may selectively che chelate iron and facilitate its utilization by the microbial cell. As such, these compounds may serve as factors of virulence that enable a microbial species to acquire iron in body tissues and fluids. Experiments will be carried out to determine the role of a siderophore produced by Histoplasma capsulatum in the establishment of experimental disease. The siderophore will be purified, by extraction and chemically characterized to determine its amino acid content, and spectra by nuclear magnetic resonance, and infrared spectroscopy. The ability to serve as a growth factor for heterologous organisms (bacteria and fungi) will be determined in plate culture. Also, the effect of siderophores from other organisms to stimulate growth of Histoplasma will be determined. The role of the Histoplasma siderophore in histoplasmosis will be studied. Growth of the organism in serum (normal, hyperferremic, and supplemented with siderophore) will be determined by plate count of yeast phase cells. An attempt will be made to correlate virulence (LD50) with ability of Histoplasma to produce siderophore in culture. The effect of siderophore and iron experimental histoplasmosis in mice will be determined and should give an indication of the relative importance of the two in establishment of disease.